Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome

ABSTRACT CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Esketamine Combined with Propofol TCI versus Propofol TCI for Deep Sedation during Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Prospective, Randomized, and Controlled Trial.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an invasive procedure that required deep sedation to suppress coughing and body movements. Deep sedation, on the other hand, has been shown to cause respiratory and circulatory depression, especially when the airway is shared with the endoscopist. Esketamine is a novel sedative and analgesic with little respiratory inhibition that appears to be an appropriate adjuvant in propofol sedation for EBUS-TBNA. We compared the efficacy and safety of esketamine combined with propofol target-controlled infusion (TCI) and propofol TCI for deep sedation in EBUS-TBNA. Methods: The study included 135 patients with ASA II-III undergoing EBUS-TBNA. They were randomly divided into two groups (group E and group P). Both groups received midazolam (0.01-0.03 mg/kg) and oxycodone (0.07-0.08 mg/kg). Then, patients in group E received 0.3 mg/kg esketamine, propofol TCI, and 0.2 mg·kg-1·h-1 esketamine for sedative maintenance. Patients in group P received only propofol TCI. The primary outcome was the dose of 1% lidocaine administrated by the endoscopist and the times of lidocaine sprays. Secondary outcome indicators were cough score, propofol dosage, patient satisfaction, endoscopist satisfaction, the incidence of sedation-related adverse effects and side effects, and recovery time. Results: Patients in group E were given significantly less lidocaine (4.36 ml/h (2.67-6.00) vs 6.00 ml/h (4.36-7.20), P < 0.001) and less spraying frequency (2.18 times/h (1.33-3.00) vs 3.00 times/h (2.18-3.60), P < 0.001) than group P. There was a statistically significant difference in cough score between the two groups (group E 2 (0-4) vs group P 3 (2-4), P=0.03). Also, mean arterial pressure (MAP) was higher in group E in the 30th min (T5, 84.10 ± 12.91 mmHg versus 79.04 ± 10.01 mmHg, P=0.012) and 40th min (T6, 87.72 ± 15.55 mmHg versus 82.14 ± 10.51 mmHg, P=0.026). There were no significant differences between the two groups in terms of sedation-related adverse events and side effects, recovery time, endoscopist satisfaction, and patient satisfaction. Conclusions: In patients with ASA II-III, esketamine as an adjuvant in combination with propofol TCI deep sedation for EBUS-TBNA can improve the sedation effect, reduce coughing reaction during the procedure, and obtain more stable blood pressure. No reduction in the occurrence of sedation-related side effects was observed. This trial is registered with ChiCTR2200061124.

Risk Factors Analysis of Phantom Limb Pain in Amputees with Malignant Tumors.

Purpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees' quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model. Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors. Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834. Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.

Preservation of superior laryngeal nerve in transoral surgery: A technology to enhance the recovery of swallowing function after surgery of hypopharyngeal carcinoma.

OBJECTIVES: We intended to preserve the internal branch of superior laryngeal nerve in transoral surgery of hypopharyngeal squamous cell carcinoma and observe swallowing function recovery. METHODS: 26 patients with hypopharyngeal squamous cell carcinoma underwent transoral surgery with the preservation of internal branch of superior laryngeal nerve. Sensation in the pharyngolaryngeal mucosa was tested by flexible laryngoscope and swallow function was evaluated by water swallow test and MD Anderson Dysphagia Inventory questionnaire after surgery. RESULTS: Surgeries were successfully performed in all patients. The internal branch of superior laryngeal nerve were preserved in all patients. Testing of mucosa sensation revealed the presence of the cough reflex in most patients. The water swallow test showed that 12 cases (46.15%) on the 1st day, 23 cases (88.46%) on the 7th day and 25 cases (96.15%) on the 14th day after operation had normal swallowing function. The mean score of MD Anderson Dysphagia Inventory was 98 on the 14th day after operation. All patients achieved an oral soft diet at a median of 3 days (range, 2-6 days), full normal oral diet at a median of 5.5 days (range, 4-10 days) and removal of the nasogastric tube at a median of 6 days (range, 5-11 days). During the two-year follow-up, 3 patients recured, 1 patient died of lung metastasis. CONCLUSIONS: Preserving of the internal branch of superior laryngeal nerve in transoral surgery is feasible, and it can help to achieve a satisfactory recovery of the swallowing function after surgery of hypopharyngeal squamous cell carcinoma.

Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites.

OBJECTIVE: This study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites. METHODS: Patients bitten by a Chinese cobra (Naja atra) (n = 50) that met the inclusion criteria were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group received regular as well as anti-snake venom serum blocking treatment, whereas regular treatment plus chymotrypsin blocking therapy was given to the control group. The necrotic volumes around snake wounds in these groups were detected on the first, third and seventh days. On the third day of treatment, some local tissues in the wounds were randomly selected for pathological biopsy, and the necrosis volume of the local tissue was observed. Furthermore, the amount of time required for wound healing was recorded. RESULTS: On the third and seventh days post-treatment, the necrotic volume of the wound of the experimental group was much smaller than that of the control group, and the experimental group's wound healing time was shorter than that of the control group (all p < 0.05). Moreover, the pathological biopsies taken from the control group showed nuclear pyknosis, fragmentation, sparse nuclear density, and blurred edges, and the degree of necrosis was much higher than that of the experimental group. CONCLUSIONS: Anti-snake venom blocking therapy is a new and improved therapy with good clinical effect on local tissue necrosis caused by Chinese cobra bites; moreover, it is superior to conventional chymotrypsin blocking therapy in the treatment of cobra bites. It can better neutralize and prevent the spread of the toxin, reduce tissue necrosis, and shorten the course of the disease by promoting healing of the wound. Furthermore, this treatment plan is also applicable to wound necrosis caused by other snake toxins, such as tissue necrosis caused by elapidae and viper families. CLINICAL TRIAL REGISTRATION: This trial is registered in the Chinese Clinical Trial Registry, a primary registry of International Clinical Trial Registry Platform, World Health Organization (Registration No. ChiCTR2200059070; trial URL:http://www.chictr.org.cn/edit.aspx?pid=134353&htm=4).

Chaihu Shugan powder alleviates liver inflammation and hepatic steatosis in NAFLD mice: A network pharmacology study and in vivo experimental validation.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common metabolic disease and is intertwined with cardiovascular disorders and diabetes. Chaihu Shugan powder (CSP) is a traditional Chinese medicine with a significant therapeutic effect on metabolic diseases, such as NAFLD. However, its pharmacological mechanisms remain to be elucidated. Methods: The main compounds of CSP were measured using LC-MS/MS. A network pharmacology study was conducted on CSP. Its potential active ingredients were selected according to oral bioavailability, drug similarity indices, and phytochemical analysis. After obtaining the intersected genes between drug targets and disease-related targets, the component-disease-target network and protein-protein interaction analysis were visualized in Cytoscape. GO and KEGG enrichment analyses were performed using the Metascape database. Six-week-old male C57BL/6 mice fed a high-fat high-fructose diet for 16 weeks plus chronic immobilization stress for 2 weeks, an in vivo model, were administered CSP or saline intragastrically. Liver histology, triglyceride and cholesterol levels, ELISA, and RT-PCR were used to assess hepatic inflammation and steatosis. Immunohistochemistry and western blotting were performed to assess protein levels. Results: A total of 130 potential target genes in CSP that act on NAFLD were identified through network pharmacology assays, including tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin-1ß (IL-1ß), and peroxisome proliferator-activated receptor γ (PPARG). KEGG enrichment analysis showed that the main pathways were involved in inflammatory pathways, such as the TNF and NF-κB signaling pathways, and metabolism-related pathways, such as the MAPK, HIF-1, FoxO, and AMPK signaling pathways. The results in vivo showed that CSP ameliorated liver inflammation and inhibited hepatic fatty acid synthesis in the hepatocyte steatosis model. More specifically, CSP therapy significantly inhibited the expression of tumor necrosis factor α (TNFα), accompanied by a decrease in TNF receptor 1 (TNFR1) and the ligand availability of TNFR1. Conclusion: Through the combination of network pharmacology and in vivo validation, this study elucidated the therapeutic effect of CSP on NAFLD, decreasing liver inflammation and inhibiting hepatic fatty acid synthesis. More specifically, the anti-inflammatory action of CSP was at least partially mediated by inhibiting the TNFα/TNFR1 signaling pathway.

Malakoplakia of Larynx: A Case Report and Literature Review of Localized Malakoplakia of Larynx.

BACKGROUND: Malakoplakia is a very rare benign granulomatous disease, which can invade multiple organ systems, and is often related to bacterial infection and weak immunity. It is rarely occurred in the larynx, once this happens, the patient would complain of cough, hoarseness, dysphagia, and even dyspnea. METHODS: We reported a case of malakoplakia of larynx. The patient complained of hoarseness and cough. Her lesion was located in the right false vocal cord. six case reports of malacoplakia in larynx were compiled from the literature and integrated with this case report. RESULTS: After excising the tumor, the symptoms of the patient with cough, hoarseness and dysphagia were improved, and there was no recurrence during 1-year follow-up. The postoperative pathological diagnosis is malakoplakia. We found that malacoplakia is more commonly located in the supraglottic region, and we speculate that there may be a relationship between larynx-associated lymphoid tissue (LALT) and laryngeal malakoplakia. The effect of surgical treatment for laryngeal malacoplakia is satisfactory. CONCLUSION: Malakoplakia of the larynx is rare. Bacterial infection, immune deficiency, and the distribution of LALT may be related to the pathogenesis and supraglottic localization of malakoplakia. The symptoms are related to the location and size of the mass and may be serious and fatal. Surgery is an important treatment for preserving laryngeal function and low recurrence rate.

Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells.

Shenmai injection (SMI) is a patented traditional Chinese medicine that is extracted from Panax ginseng and Ophiopogon japonicus and is commonly used to treat cardiovascular diseases and tumors. The O. japonicus extract Ophiopogonin D' (OPD') is highly cardiotoxic. Mitochondria are central to OPD'-induced cardiotoxicity, although the precise mechanisms remain unclear. Excessive mitophagy activation and mitochondrial dysfunction lead to apoptosis, and the PTEN-induced kinase 1(PINK1)/Parkin pathway is critical in regulating mitophagy and mitochondrial function. We investigated the role of the PINK1/Parkin pathway in OPD'-induced mitochondrial damage and cardiotoxicity in AC16 cells. Concentrations of 2 µM OPD' and above inhibited cardiomyocyte viability and increased lactate dehydrogenase (LDH) release in a concentration- and time-dependent manner. OPD' was toxic to cells and mitochondria and increased the rate of apoptosis, triggering pyknosis, decreasing mitochondrial membrane potential (MMP), and decreasing the protein expression of the biogenesis regulator peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α). The increased ratio of microtubule-associated proteins 1 A/1B light chain 3B (LC3-II/LC3-I) in mitochondria indicated that OPD' induced mitophagy. OPD' significantly induced oxidative stress and apoptosis, including increased reactive oxygen species (ROS) generation and decreased nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1(HO-1), and B-cell lymphoma 2 (Bcl-2) protein expression. OPD' activated the PINK1/Parkin pathway and promoted PINK1/Parkin translocation to mitochondria. Inhibiting mitophagy attenuated OPD'-induced PINK1/Parkin pathway activation and preserved mitochondrial biogenesis, consequently mitigating OPD'-induced mitochondrial dysfunction and apoptosis. These findings suggest that OPD'-induced cardiomyocyte mitophagy and mitochondrial damage are at least partially mediated by dysregulation of the PINK1/Parkin pathway.

Circ_0000523 regulates miR-1184/COL1A1/PI3K/Akt pathway to promote nasopharyngeal carcinoma progression.

BACKGROUND: The present study is to investigate the biological functions and mechanisms of circular RNA_0000523 (circ_0000523) in nasopharyngeal carcinoma (NPC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of circ_0000523 and microRNA-1184 (miR-1184) in NPC tissues and cells. Collagen type 1 alpha 1 chain (COL1A1) expression was assessed by qRT-PCR and immunohistochemistry (IHC) assay. Cell proliferation, cell cycle progression, migration and invasion were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry and Transwell assays. Xenograft nude mouse models were used to investigate the metastatic potential of NPC cells in vivo. The binding relationships between circ_0000523 and miR-1184, and between miR-1184 and COL1A1 were detected by dual-luciferase reporter gene assay. The protein expressions of COL1A1, phosphatidylinositol 3-kinase (p85), phosphorylated (p)-p85, protein kinase B (Akt) and p-Akt were detected through Western blot. The DAVID database was used for the enrichment analysis of the potential targets of miR-1184. RESULTS: Circ_0000523 and COL1A1 mRNA expressions were significantly increased in NPC tissues and cell lines. Circ_0000523 overexpression promoted NPC cell proliferation and accelerated cell cycle progression, whereas miR-1184 overexpression reversed these effects; circ_0000523 knockdown suppressed NPC cell proliferation and induced cell cycle arrest, while miR-1184 inhibition counteracted these effects. MiR-1184 was the downstream target of circ_0000523, and COL1A1 was the target gene of miR-1184 and could be positively modulated by circ_0000523. COL1A1 overexpression increased the expression levels of p-p85 and p-Akt, whereas knocking down COL1A1 repressed their expressions. CONCLUSIONS: Circ_0000523 facilitates NPC progression through regulating the miR-1184/COL1A1 axis.

A self-delivery chimeric peptide for high efficient cell membrane-targeting low-temperature photothermal/photodynamic combinational therapy and metastasis suppression of tumor.

Cellular barriers such as the cell membranes, lysosomes or nuclear pores of tumor cells hinder the drugs delivery and weaken the efficiency of traditional tumor therapies. Targeted destructing tumor cell membranes can quickly destroy cell homeostasis and kill cells without facing intracellular delivery barriers. Herein, we designed a self-delivery phototherapeutic chimeric peptide (CCP) for high efficient cell membrane-targeting combinational low-temperature photothermal therapy (LTPTT) and photodynamic therapy (PDT). The self-assembled CCP nanoparticles display remarkable tumor accumulation after systemic administration without additional carriers, avoiding the carriers related side toxicities. The CCPs are able to generate reactive oxygen species (ROS) and mild heat (<45 °C) locally at cell membrane and quickly induce immunogenic cell death to achieve efficient combinational LTPTT/PDT. The damage-associated molecular patterns released after cell membrane rupture effectively elicit antitumor immunity to eradicate residual tumor cells. With a single dosage and short-term near-infrared (NIR) light irradiation, CCPs significantly inhibit growth and metastasis of tumor, and prolong survival time of tumor-bearing mice. This work presents a unique cell membrane-targeting phototherapy strategy to kill tumor and suppress metastasis in an effective, safe and minimally invasive manner.

Changes in laryngopharyngeal reflux after uvulopalatopharyngoplasty for obstructive sleep apnea: An observational study.

PURPOSE: To estimate laryngopharyngeal reflux (LPR) changes after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) using the reflux symptom index (RSI) and reflux finding score (RFS) questionnaires. METHODS: A total of 91 participants were recruited and divided into three groups: control (n = 27), OSA mild to moderate (n = 29), and OSA severe (n = 35) groups according to polysomnography. All participants completed the preoperative RSI, and underwent blinded evaluation on videolaryngoscopy using the RFS questionnaire. Thirty-four OSA patients who underwent UPPP surgery completed postoperative polysomnography and questionnaires again after a 6-month follow-up. RESULTS: The RSI score and RFS were higher in patients with OSA than in those without OSA. Patients with severe OSA also had a higher RSI score and RFS than those with mild to moderate OSA. Apnea and hypopnea index degree and percentage of recording time for <90% oxygen saturation showed positive correlation with LPR symptoms. But the lowest blood oxygen saturation during the recording time was negatively correlated with LPR symptoms. The mean RSI score and RFS before UPPP surgery were 15.88 ± 4.85 and 13.18 ± 4.80, after surgery decreasing to 9.53 ± 4.16 and 8.65 ± 4.87, respectively (P <.05). In 25 patients where surgery was successful, RSI scores, RFSs and individual RSI variables decreased after surgery. CONCLUSIONS: LPR symptoms are common among OSA patients, and the coexistence of OSA and LPR cannot be ignored. Successful UPPP surgery potentially reduces LPR symptoms and improves laryngoscopic signs by alleviating sleep respiratory disorders. Level of Evidence: 3.

Autophagy-inhibiting biomimetic nanodrugs enhance photothermal therapy and boost antitumor immunity.

The instinctive protective stress responses of tumor cells hamper low-temperature photothermal therapy (LTPTT), resulting in tumor recurrence and metastasis. The rapid blood clearance and low-efficiency tumor enrichment of nanomedicines also decrease the efficacy of LTPTT. In this study, we fabricated coassembled photothermal agents (indocyanine green, ICG) and autophagy inhibitors (chloroquine, CQ) and red blood cell and cancer cell hybrid membrane (RCm)-camouflaged ICGCQ@RCm nanoparticles (ICGCQ@RCm NPs) to enhance tumor LTPTT. The ICGCQ@RCm NPs exhibited prolonged blood drug circulation and markedly enhanced drug accumulation in tumor tissues. The ICGCQ@RCm NPs reduced the thermal tolerance of tumor cells to sensitize ICG-mediated LTPTT by inhibiting protective autophagy. The ICGCQ@RCm NPs exerted strong immunogenic cell death (ICD) after efficient LTPTT to activate antitumor immunity. In addition, ICGCQ@RCms optimized the therapeutic efficacy by imaging-guided LTPTT, taking advantage of the near-infrared (NIR) fluorescence of ICG. Consequently, the ICGCQ@RCm NPs effectively inhibited tumors under mild LTPTT, significantly suppressed tumor metastasis and prolonged the survival time of tumor-bearing mice. Furthermore, the ICGCQ@RCm NPs showed high biosafety in vitro and in vivo. The ICGCQ@RCm NPs demonstrated tumor-targeting and imaging-guided autophagy inhibition-sensitized LTPTT using two Food and Drug Administration (FDA)-approved drugs, which have great potential for clinical application.

Versatile Nanodrugs Containing Glutathione and Heme Oxygenase 1 Inhibitors Enable Suppression of Antioxidant Defense System in a Two-Pronged Manner for Enhanced Photodynamic Therapy.

The antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)-based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l-buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO-1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two-pronged manner. BSO reduces intracellular glutathione levels to minimize ROS elimination and protein protection during PDT, and ZnPP inhibits the ROS-stimulated upregulation of the antioxidant HO-1, thus preventing ROS removal by cells after PDT. Thus, BSO and ZnPP synergistically suppress the antioxidant defense systems of cancer cells both during and after protoporphyrin-IX-mediated PDT in a two-pronged manner, resulting in tumor cell death through excess oxidative pressure. The results demonstrate that the construction of nanodrugs having dual antioxidation defense suppression properties is a promising route for the development of highly efficient ROS-based therapies.

Clinical significance of neuropilin-2 expression in laryngeal squamous cell carcinoma.

PURPOSE: The purpose of the study is to evaluate the expression of NRP-2 and explore its role in Laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: NRP-2 expression in 70 primary LSCC tissue specimens were analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients´ survival rate. Additionally, 9 paired LSCC tissues were evaluated for NRP-2 expression by Western blotting. RESULTS: The Western blotting indicated that NRP-2 expression levels in LSCC were significantly higher than those in the paraneoplastic tissues (P < 0.05). Immunohistochemistry staining revealed that NRP-2 was detected in all primary tumor samples, moreover, high expression of NRP-2 was significantly correlated with TNM stage (P < 0.05), clinical stage (P < 0.05), histological classification (P < 0.05), lymph node metastasis (P < 0.05) and recurrence (P = 0.001). Survival curves determined by the Kaplan-Meier method showed that high expression of NRP-2 can reduce overall survival (both group P < 0.05). Then we combined the NRP-2 expression and lymph node status, and Kaplan-Meier survival showed patients with high expression of NRP-2 or lymph node metastasis (+) had both shorter disease-free and overall survival than others (both P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that histological grade (P = 0.045), lymph node metastasis (P = 0.020) and high expression of NRP-2 (P = 0.033) were statistically significant, independent predictor of prognosis. CONCLUSIONS: NRP-2 may contribute to LSCC progression and represents as a novel prognostic indicator as well as a potential therapeutic target for LSCC.

Screening bioactive components of Glycyrrhiza uralensis Fisch. with isolated perfused lung extraction and HPLC-ESI-MSn analysis.

The isolated perfused rat lung (IPL), coupled with high performance liquid chromatography\tandem mass spectrometry analysis (HPLC-ESI-MSn), has been developed as a tool for screening bioactive components in Glycyrrhiza uralensis Fisch. (GU). First, IPL was perfused with the water extract of GU (EGU), the bioactive components in the EGU would selectively combine to the receptors or channels of lung. By changing the pH of perfused solution, the combined components were eluated and then detected by HPLC-ESI-MSn. Four compounds were detected in the desorption eluate of IPL, among these compounds, liquiritin (1), ononin (2) and glycyrrhizic acid (4) were identified by comparing with the chromatography of the standards, while licorice-saponin G2 (3) were determined by analysis of the structure clearage characterization of mass spectrometry. Then, due to the lack of compound 3 sample, compounds 1, 2 and 4 with respective concentrations of 50 µM, 5 µM, 500 nM, 50 nM and 5 nM were applied to evaluate the protective effect of pulmonary epithelial cells (PEC, A549 cell) injury induced by lipopolysaccharide (LPS) for anti-inflammatory activity assessment. The results showed that except the 5 nM group of compound 1, 5 nM and 50 nM groups of compound 2, all other groups could remarkably inhibit the PEC injury (vs LPS group, 2-500 nM groups: p < 0.05; other groups: p < 0.01), all compound showed the dose-dependent effect. In conclusion, IPL coupled with HPLC-ESI-MSn was successfully used to screen the anti-inflammatory components of GU for the first time. The application of IPL coupled with HPLC-ESI-MSn for screening bioactive components of TCMs is rapid, convenient and reliable, and the isolated perfused technology could be extended to isolated heart, liver, kidney, and so on.

Correlation of early postoperative blood glucose levels with postoperative complications, hospital costs, and length of hospital stay in patients with gastrointestinal malignancies.

Early postoperative hyperglycemia in non-diabetic patients is an important risk factor affecting postoperative complications and mortality. This study aimed at investigating the effects of early postoperative hyperglycemia on postoperative complications, hospital costs, and length of hospital stay in non-diabetic patients with gastrointestinal malignancies; data of 1,015 non-diabetic patients with gastrointestinal malignancies, who underwent surgical intervention between January 2010 and January 2012, were retrospectively evaluated. Records on fasting plasma glucose (FPG), liver function, and kidney function were collected before and one day after surgery. Correlation of early postoperative FPG levels with postoperative complications, hospital costs, and length of hospital stay was further assessed in non-diabetic patients with gastrointestinal malignancies. One day after surgery, FPG results were significantly increased compared to preoperative values. FPG levels greater than or equal to 9.13 mmol/L (or 164.34 mg/dL) were associated with significant increases in the incidence of postoperative complications, length of hospital stay, and hospital costs. An association is shown between FPG and postoperative hyperglycemia in non-diabetic patients undergoing surgery for gastrointestinal malignancies. Significant increases in postoperative complications among these patients suggest that measurement of early postoperative FPG levels is critical to identify patients with postoperative hyperglycemia.